3-71473959-C-T

Variant names:

• chr3-71473959-C-T
• rs9819066
• NM_001349338.3:c.-168+19467G>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001349338.3(FOXP1):​c.-168+19467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 151,988 control chromosomes in the GnomAD database, including 9,990 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (9990 hom., cov: 32)
• Consequence: FOXP1 NM_001349338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

Genes affected

FOXP1 (HGNC:3823): (forkhead box P1) This gene belongs to subfamily P of the forkhead box (FOX) transcription factor family. Forkhead box transcription factors play important roles in the regulation of tissue- and cell type-specific gene transcription during both development and adulthood. Forkhead box P1 protein contains both DNA-binding- and protein-protein binding-domains. This gene may act as a tumor suppressor as it is lost in several tumor types and maps to a chromosomal region (3p14.1) reported to contain a tumor suppressor gene(s). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

ENSG00000285708 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FOXP1	NM_001349338.3	c.-168+19467G>A		intron_variant	Intron 3 of 20	ENST00000649528.3	NP_001336267.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FOXP1	ENST00000649528.3	c.-168+19467G>A		intron_variant	Intron 3 of 20		NM_001349338.3	ENSP00000497369.1
ENSG00000285708	ENST00000647725.1	c.-290+19467G>A		intron_variant	Intron 7 of 25			ENSP00000497585.1

Frequencies

GnomAD3 genomes AF: 0.355 AC: 53870 AN: 151870 Hom.: 9979 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.397

Gnomad EAS AF: 0.00597

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.382

Gnomad OTH AF: 0.362

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.355 AC: 53902 AN: 151988 Hom.: 9990 Cov.: 32 AF XY: 0.350 AC XY: 26010 AN XY: 74282

Gnomad4 AFR AF: 0.372

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.397

Gnomad4 EAS AF: 0.00599

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.386

Gnomad4 NFE AF: 0.382

Gnomad4 OTH AF: 0.357

Alfa AF: 0.373 Hom.: 15756

Bravo AF: 0.343

Asia WGS AF: 0.153 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.49
DANN	Benign	0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9819066; hg19: chr3-71523110;